Intradermal immunization by Ebola virus GP subunit vaccines using microneedle patches protects mice against lethal EBOV challenge

Ying Liu,Ling Ye,Fang Lin,Yasmine Gomaa,David Flyer,Ricardo Carrion,Jean L Patterson,Mark R Prausnitz,Gale Smith,Gregory Glenn,Hua Wu,Richard W Compans,Chinglai Yang

doi:10.1038/s41598-018-29135-w

Ying Liu, Ling Ye + Show 11 more

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https://doi.org/10.1038/s41598-018-29135-w

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Development of a safe and efficacious filovirus vaccine is of high importance to public health. In this study, we compared immune responses induced by Ebola virus (EBOV) glycoprotein (GP) subunit vaccines via intradermal immunization with microneedle (MN) patches and the conventional intramuscular (IM) injection in mice, which showed that MN delivery of GP induced higher levels and longer lasting antibody responses against GP than IM injection. Further, we found that EBOV GP in formulation with a saponin-based adjuvant, Matrix-M, can be efficiently loaded onto MN patches. Co-delivery of Matrix-M with GP significantly enhanced induction of antibody responses by MN delivery, as also observed for IM injection. Results from challenge studies showed that all mice that received the GP/adjuvant formulation by MN or IM immunizations were protected from lethal EBOV challenge. Further, 4 out of 5 mice vaccinated by MN delivery of unadjuvanted GP also survived the challenge, whereas only 1 out of 5 mice vaccinated by IM injection of unadjuvanted GP survived the challenge. These results demonstrate that MN patch delivery of EBOV GP subunit vaccines, which is expected to enable improved safety and thermal stability, can confer effective protection against EBOV infection that is superior to IM vaccination.

Highlights

Ebola virus (EBOV) is an enveloped, negative single-stranded RNA virus that belongs to the Filoviridae family[1]
The focus of the present study is to investigate the utility of MN patches for vaccination with an EBOV GP subunit vaccine for the development of an effective and potentially thermally stable EBOV vaccine strategy
Our results show that GP subunit vaccines can be successfully coated onto the solid-metal MN patches, and that the GP molecules retained their molecular integrity during the process of GP-MN preparation

Summary

Introduction

Ebola virus (EBOV) is an enveloped, negative single-stranded RNA virus that belongs to the Filoviridae family[1]. Results from Phase I clinical trials of influenza vaccine showed that immunization by MN patch delivery of influenza vaccines was able to induce robust immune responses in humans that are at least equivalent to vaccination by the conventional IM injection method[22]. In addition to viral vector-based EBOV vaccines, an EBOV GP subunit vaccine entered a Phase I human clinical trial in response to the 2013–2016 EBOV epidemic[15]. The EBOV GP subunit vaccine was further shown to induce protective immune responses against lethal EBOV challenge in mice when applied in formulation with a saponin-based adjuvant Matrix-M by intramuscular (IM) injection. Immunogenicity of EBOV GP vaccines on MN patches can be effectively augmented by formulating with the Matrix-M adjuvant as observed previously for IM injection of the EBOV GP nanoparticle vaccines, and can confer complete protection against lethal EBOV challenge

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